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HCV diagnostic testing

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HCV Screening - Casting the Net

  • Initial screen: HCV antibody (anti-HCV) test.
    • Detects exposure; indicates past or current infection.
    • Becomes positive 4-10 weeks post-exposure.
  • Confirmatory test (if anti-HCV positive): HCV RNA PCR.
    • Detects active, ongoing infection (viremia).
    • Essential for diagnosing chronic HCV & guiding therapy.

HCV Antibody Screening and Reflex RNA Testing Algorithm

  • Universal screening: CDC recommends one-time screening for all adults (≥18 years) and all pregnant women during each pregnancy.

⭐ Many individuals with chronic HCV are asymptomatic; universal screening is crucial for early detection and prevention of long-term complications like cirrhosis and hepatocellular carcinoma.

Serology vs RNA - The Core Tests

A two-step process is standard: screen with serology, then confirm active infection with molecular testing.

FeatureHCV Antibody (EIA)HCV RNA (PCR)
DetectsIgG antibodies to HCV proteinsThe virus's genetic material directly
IndicatesExposure to HCV (past or current)Active/current viral replication
Window PeriodPositive after 2-6 monthsPositive as early as 2 weeks
Clinical RoleInitial screening test for HCVConfirms active infection; used to monitor response to antiviral therapy
Key LimitationDoesn't differentiate active vs. resolved infectionHigher cost; not for initial mass screening

Diagnostic Algorithm - Interpreting Results

Initial screening begins with the HCV antibody (anti-HCV) test. A positive result prompts further testing to differentiate between active and resolved infection.

  • Anti-HCV Positive, HCV RNA Positive:
    • Indicates active (current) infection.
    • Patient is infectious.
  • Anti-HCV Positive, HCV RNA Negative:
    • Indicates resolved infection.
    • Can also be a false-positive anti-HCV screen.
  • Anti-HCV Negative:
    • Generally rules out HCV infection.
    • ⚠️ Exception: May be negative during the early ~2 month "window period" or in severely immunocompromised patients.

⭐ Unlike Hepatitis B surface antibody (anti-HBs), the presence of anti-HCV antibody does not confer immunity or protection against future infection.

  • Screening for HCV begins with the HCV antibody test.
  • A positive antibody test is followed by HCV RNA PCR for confirmation.
  • HCV RNA indicates active infection (acute or chronic).
  • Anti-HCV positive, RNA negative suggests a resolved infection.
  • During the window period, HCV RNA is detectable 1-2 weeks after infection, while antibodies take longer.
  • Quantitative HCV RNA helps monitor treatment response.

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